Periodontal disease or gum disease as it is often called can be defined as an infection and inflammation of the gingiva or gums and loss of underlying alveolar bone support. There are varying levels of severity of the disease with the mildest cases termed as gingivitis (inflamed and bleeding gums). More severe cases are clinically known as periodontitis and can involve loss of bone support. Gingivitis is reversible and can often be eliminated with a thorough dental prophylaxis followed by improved personal oral hygiene procedures. If gingivitis is not controlled, the disease often progresses into periodontitis.
Periodontitis is not only characterized by bacterial infection and inflammation, it is also accompanied by the formation of periodontal pockets (spaces between the teeth and gums) and bone deterioration which can lead to tooth loss. Periodontitis is recurring, progressive, and episodic. There is no cure at this time. Effective treatment is to apply professional intervention to halt disease progression.
Professional intervention may involve surgical or nonsurgical procedures. Nonsurgical treatment consists of periodic professional scaling, root planing, and soft tissue curettage, in combination with conscientious home care by brushing and flossing on the part of the patient. Surgical treatment involves gingivectomy and flap surgery to recontour the soft and hard tissue around the diseased areas.
In recent years, it has become increasingly recognized that control of periodontitis may be possible with the use of antimicrobial agents delivered to the infected site. Systemic antibiotics taken orally or intramuscularly have been successfully used, but due to the concern about allergic responses, the development of resistance, and the treatment of the whole person rather than the specific infection site, their use is recommended only in the severest of periodontal cases.
One of the most recently proposed methods of treating periodontitis with chemotherapeutic agents has involved the placement of these agents in conjunction with polymeric delivery systems directly into the periodontal pocket. These include the cellulose hollow fibers loaded with tetracycline described in U.S. Pat. No. 4,175,326 to Goodson, the ethylcellulose films loaded with metronidazole described in U.S. Pat. No. 4,568,535 to Loesche, the absorbable putty-like material described in U.S. Pat. No. 4,568,536 to Kronenthal, the ethylene vinyl acetate fibers loaded with tetracycline described in the European patent application No. 84401985.1 to Goodson, and the biodegradable microspheres and matrix described in U.S. Pat. No. 4,685,883 to Jernberg.
All of these delivery systems involve placing the product directly into the periodontal pocket and having the chemotherapeutic agent released over a time of 5 to 14 days. Because most of the chemotherapeutic agents are potent antimicrobials or antibiotics, a brief exposure at even low concentrations is sufficient to destroy any periodontal pathogen in the pocket. However, the irrigation of periodontal pockets with antimicrobial or antibiotic solutions is ineffective in controlling periodontal disease and these agents have to be delivered over a long period of time to be effective. The reason for these observations is that the bacteria responsible for periodontal disease are not all located within the periodontal pocket. If the bacteria are located within the gingival tissue as well as the pocket, then the local application of an antimicrobial will destroy the bacteria within the pocket and on the surface of the gingival tissue but not that deep within the tissue. The gingival tissue on the surface dies and is replaced with fresh tissue within a time of approximately one week. Thus, fresh tissue infected with bacteria not killed with the original treatment will repopulate the pocket and the disease continues to progress. The polymeric controlled delivery systems are effective because they continue to release the chemotherapeutic agent over a long time and prevent the repopulation of the pocket by killing the freshly exposed bacteria.
Recent research has indeed shown that the bacteria often responsible for periodontal disease exist not only in the periodontal pocket but also within the gingival tissue. This is especially true for localized juvenile periodontitis. The only way to treat this form of periodontal disease has been to administer systemic antibiotics which can attack the bacterial infection within the gingival tissue itself. Several researchers have also shown that the bacteria responsible for periodontal disease have been found in the tissue of patients with normal adult periodontitis. Thus, there is a need for a local delivery system that allows chemotherapeutic agents to destroy the bacteria within the gingival tissue as well as the periodontal pocket.
Although the polymeric controlled delivery systems placed within the periodontal pocket have been shown to be effective in treating periodontal disease, they have several problems which hinder their widespread use. Most of these systems have been fibers, films, or sponges which are difficult and time-consuming to place into the contours of a periodontal pocket. Any material exposed above the gingival margin is quickly removed by normal oral hygiene procedures such as brushing or flossing. Moreover, unless the delivery systems are adhesively bound to the tooth or the gingival tissue, they tend to be expelled from the pocket by the mechanical action of the teeth and gums during eating or by the outward flow of the gingival crevicular fluid.
One method to avoid the placement and retention problems associated with the polymeric delivery systems is to deliver the chemotherapeutic agent by itself to the periodontal pocket. However, treatment by mouth rinse and other topically applied oral medicinal agents does not allow the antibacterial agents to penetrate into the periodontal pocket where they are needed. Irrigation of the pockets with these agents has shown some effects on gingivitis, but the short time of exposure with irrigation solutions and the rapid removal of any therapeutic agent by the outward flow of the crevicular fluid make this type of treatment ineffective with severe cases of periodontitis. The one system that seems to have effectiveness is the placement of an aqueous solution of tetracycline directly into the periodontal pocket. The rationale for the effectiveness of this treatment is the adsorption of tetracycline to dentin at the base of the tooth and the subsequent sustained release over a period of about one week. Thus, tetracycline provides its own controlled release system in this instance. It does not, however, penetrate the gingival tissue to kill the bacteria located intragingivally.
Apparently tetracycline is not alone in its lack of tissue penetration. Other antimicrobials added to the periodontal pocket as aqueous solutions do not penetrate the gingival tissue deep enough to affect the bacteria located within the tissue. There is a need for a delivery system for chemotherapeutic agents that enables the agent to penetrate the gingival tissue layers sufficiently to contact and destroy all periodontal pathogens.